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Pregna-D′-pentaranes, Progestins and Antiprogestins: II. Pathways and Realization Mechanisms of Separate Biological Functions of Steroid Hormones

“…A fourteen-day introduction of 16α,17α-cyclohexanoprogesterone, a full agonist of progesterone, to puberal rats preliminarily subjected to four-day estrogenization resulted, for the majority of animals, in the morphological state of uterus very close to that at the late stage of pregnancy: thickening of the wall and the diameter of opening; enlargement of the layer of cylindrical epithelium; the appearance of multiple cilia and the formation of side branches from them; an expressed hypertrophy of the myocytes of cylindrical layer of myometrium coupled with the displacement of stroma, convergence of cells, and the creation of gap junctions between them, found by electron microscopy [19].…”

“…The destructive action of 5α-dihydropentarane (VI) on the uterine epithelium, we found, demonstrates that this phenomenon may be due to the antihormonal action of the nearest progesterone metabolites. This conclusion prompted us to return to the check of the state of uterine epithelium in the experiment on the formation of pseudopregnancy and its termination by means of (VI) and (VII) [19]. A substantial disturbance in the epithelium density was observed in the animal tissues treated with these compounds.…”

“…To a lesser degree, the effect of antagonists is extended to endometrium, which retains some signs of functionalization indicating a certain selectivity of antihormonal action of dihydropregna--pentaranes (VI) and (VII). A biochemical testing of the uterus of pseudopregnant rats indicated an extremely low concentration of PRs and, simultaneously, the absence of any other centers specifically binding the 5α-and 5β-dihydropentaranes (VI) and (VII) [19]. A very low affinity of these compounds for PR [12] suggest that the antagonistic action of such analogues of the primary progesterone metabolites can be considered to be a manifestation of partial antagonism that is independent of the cytosol PR and is directed at the inhibition of one of the progesterone functions, namely, the stimulation of hypertrophy of myometrium cells.…”

“…Therefore, we became interested in the presence of any other manifestations of the effects of these compounds as the analogues of the nearest metabolites of the native hormone. In fact, the introduction of (VI) to intact virgin female rats leads only to a destruction of epithelium, which manifests itself in the loss of ordered arrangement of cells and a decrease in the thickness of their layer in it [21].…”